Immunotherapy: A Paradigm Shift in Cancer Treatment

Analyzing cancer treatment requires understanding the evolution of chemotherapy. First-generation chemotherapies are highly toxic drugs that serve as physicians’ first-line defense against rapidly proliferating cancer cells. Treatment regimens using these therapeutics were typically specific to the tumor’s location — for example, breast cancer was treated differently than brain cancer. More recently, scientists have learned that not all breast cancers look the same, and in fact, certain subtypes of breast cancer more closely resemble cancers in others areas of the body. These similarities are largely attributable to overlapping genetic mutations that created the tumor. This realization resulted in efforts to reclassify tumor subtypes and elucidate the role of genomics in cancer development, progression and metastasis. This work has been a public/private partnership, with the US government allocating billions of dollars toward initiatives such as the Human Genome Project, and pharmaceutical companies investing >$9 billion annually on genetic-based research and development. These investments yielded a second generation of chemotherapies called targeted therapeutics. Targeted therapeutics provide many benefits, such as improved survival and reduced toxicity. However, these incremental improvements in our fight against cancer have left scientists wondering whether this “more of the same” approach will lead to diminishing marginal returns over time…

Figure 1: Example of Diminishing Marginal Returns

A massive need exists for disruptive innovation, and luckily, disruptive innovation is here. On the rise is a new class of cancer treatment: immunotherapy, which has the potential to impact oncology in the way penicillin impacted treatment of infections.

Figure 2: Actual Footage of Immunotherapies at Work Killing Tumor Cells

What is immunotherapy? Rather than attacking the cancer directly, as chemotherapy does, immunotherapy rallies the patient’s own immune system to fight the disease.

Figure 3: “You are Beaten. It is Useless to Resist” — Darth Vader

There are many potential benefits to immunotherapy. It uses the patient’s own cells to attack the cancer, which limits the harmful side-effects of other curative procedures. It can also be more effective in killing all cancer cells, including metastatic cells, circulating tumor cells, and tumors caused by seeding during biopsy. And it can be more powerful. Through billions of years of evolution, our immune system has developed formidable tools to attack and kill invading cells if given the opportunity. As Russell Crowe would say…

Figure 4: Maximus Decimus Meridius’ Thoughts on Immunotherapies

Two promising new immunotherapies have been paving the way: Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo.

Keytruda and Opdivo are both checkpoint inhibitors which target the PD-1 protein. Keytruda and Opdivo enable killer T-cells, white blood cells often described as the soldiers of the immune system. T-cells are so fierce that they have built-in brakes — so-called checkpoints — to prevent them from attacking normal tissue. Cancerous cells express these checkpoints, allowing them to hide from the immune system. As the name suggests, a checkpoint inhibitor blocks the checkpoints so that T-cells can find the cancer and destroy it.

Immunotherapies are also specific to cancer subtypes, as opposed to a location in the body, targeting the underlying mutation that caused healthy tissue to transform into a rogue tumor. Keytruda has received FDA approval to treat any unresectable or metastatic solid tumor in patients exhibiting microsatellite instability (MSI-H) or DNA mismatch repair deficiencies (dMMR), and Opdivo has received similar approval for certain applications. These approvals mark the first instances of drugs receiving FDA approval based on common biomarkers rather than the tumor location, further signaling the future for this new class of cancer treatment, and more broadly, precision medicine.

Immunotherapies have massive implications for gastrointestinal health. Approximately 15% of all colorectal cancers develop via microsatellite instability. Further, there is potential for immunotherapies to treat autoimmune disorders, such as Crohn’s disease and ulcerative colitis. Finally, immunotherapies could also be used to normalize dysregulated immune systems that have been implicated in diseases such as necrotizing enterocolitis (NEC) and graft-versus-host disease (GvHD). Diagnostic tests will play an important role in testing and developing these new therapies, identifying patient populations who will be most relevant for these new types of precision therapeutics, and monitoring the patient’s immune response to treatment. Geneoscopy is at the forefront of this revolution, and we look forward to providing tests and services that help patients leverage the power of this paradigm shift in cancer treatment.

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